Michael N L, Chang G, d'Arcy L A, Ehrenberg P K, Mariani R, Busch M P, Birx D L, Schwartz D H
Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, MD 20850, USA.
J Virol. 1995 Jul;69(7):4228-36. doi: 10.1128/JVI.69.7.4228-4236.1995.
We have been studying a patient who acquired human immunodeficiency virus (HIV) infection via a blood transfusion 13 years ago. She has remained asymptomatic since that time. The blood donor and two other recipients have all died of AIDS. Although this patient has shown persistently strong seroreactivity to HIV type 1 (HIV-1) antigens by Western blot (immunoblot), she has been continually HIV culture negative in results from multiple laboratories over the last 6 years and has a very low viral burden. Her CD4+ T-cell count has fluctuated around a mean of 399 cells per microliters, with little change in lymphocyte subset percentages. Strong cellular immune responses to HIV-1 epitopes by this patient have been demonstrated. We now report the results of an intensive molecular genetic analysis of the HIV-1 proviral quasispecies from this patient sampled over 5 years. Long terminal repeat region sequences supported the argument for normal basal and Tat-mediated promoter activities. Sequential sequencing of the nef gene revealed a low frequency (8.3%) of defective genes and a striking lack of sequence evolution. Functional analysis of predominant nef genes by both a cell surface CD4 downregulation and a viral infectivity complementation assay showed wild-type function. In contrast, sequential analysis of an amplicon containing the vif, vpr, vpu, tat1, and rev1 genes revealed the presence of inactivating mutations in 64% of the clones. These data suggest that this patient, initially infected with a virulent swarm of HIV-1, is presently infected with a more-attenuated viral quasispecies as a result of effective host immunity.
我们一直在研究一名患者，她在13年前因输血感染了人类免疫缺陷病毒（HIV）。自那时以来，她一直没有症状。献血者和另外两名受血者均死于艾滋病。尽管该患者通过蛋白质印迹法（免疫印迹法）对1型HIV（HIV-1）抗原持续表现出强烈的血清反应性，但在过去6年中，多个实验室的HIV培养结果一直为阴性，且病毒载量极低。她的CD4 + T细胞计数围绕每微升399个细胞的平均值波动，淋巴细胞亚群百分比变化不大。已证明该患者对HIV-1表位有强烈的细胞免疫反应。我们现在报告对该患者5年来采集的HIV-1前病毒准种进行深入分子遗传学分析的结果。长末端重复序列区域的序列支持了关于正常基础和Tat介导的启动子活性的观点。对nef基因进行连续测序发现缺陷基因的频率较低（8.3%），且序列缺乏明显进化。通过细胞表面CD4下调和病毒感染性互补试验对主要nef基因进行功能分析，结果显示其具有野生型功能。相比之下，对包含vif、vpr、vpu、tat1和rev1基因的扩增子进行连续分析发现，64%的克隆存在失活突变。这些数据表明，该患者最初感染的是一群毒性较强的HIV-1，由于有效的宿主免疫，目前感染的是一种毒性较弱的病毒准种。
